This is a multidisciplinary investigation of the pathogenic mechanisms and specific immunologic aspects of the capsular polysaccharide of the clinically most important anaerobic species, Bacteroides fragilis. Our prior studies have demonstrated that the capsular polysaccharide causes the major pathologic sequelae of infection with this organism - absence formation. The proposal will utilize known techniques of carbohydrate chemistry to prepare polysaccharides, chemically modified polysaccharides and oligosaccharides. These carbohydrates will be tested for virulence in a well-developed animal model of intraabdominal sepsis which closely mimics the process in humans. Understanding the mechanisms of abscess formation should provide insight into virulence mechanisms of other organisms which induce this classical host response. Our work with this polysaccharide has shown that prior immunization prevented abscess formation and is dependent on the presence of T cells. There is increasing evidence for the role of T cells in immunity to bacterial polysaccharides. These studies should provide insight into which carbohydrate determinants are responsible for T cell activation, how T cells interest with polysaccharides in general, the genetic control of those responses and the T cell subsets involved. B. fragilis is a major cause of bacteremia in humans. Our prior studies have shown that immunity to bacteremia (as opposed to abscess formation) is antibody-dependent. We shall investigate the humoral host defense mechanisms against B. fragilis. Specific issues to be addressed include the interaction between antibody and complement for killing this organism. In summary, this is a multidisciplinary approach to investigate bacterial virulence and host-parasite interactions focusing on an important human pathogen. The majority of current interest in bacterial polysaccharides concentrates on vaccine development. In our study we are investigating the basic issues involved in the interaction between these carbohydrates and the host. An understanding of these mechanisms should provide insight and guidance to the development of bacterial vaccines and the modulation of host responses in the future.